Reperfusion injury of the ischemic myocardium is characterized by overproduction of oxygen and nitrogen derived free radicals and oxidants. Some of the final common pathways of reperfusion injury include the production of the toxic oxidant peroxynitrite, the free radical nitric oxide, and the prostaglandin thromboxane. Inotek, Inc. has developed an agent, mercaptoethylguanidine (MEG), which interferes with all 3 pathways simultaneously, acting as a potent scavenger of peroxynitrite, inhibitor of cyclooxygenase, and selective inhibitor of the inducible nitric oxide synthase. The overall goal of this Phase I SBIR proposal is to establish whether MEG prevents cellular injury in an experimental model of myocardial infarction and reperfusion. This hypothesis will be tested using well-established rat models of myocardial ischemia- reperfusion. Demonstration that MEG prevents tissue injury in this model would represent a breakthrough in the design of novel therapeutic regimens for reperfusion injury and would justify continued commercial development of MEG. Phase II SBIR funding would be used to support pre-clinical toxicology, pathology and clinical studies.